Is Pyridoxal-5-Phosphate (P5P) the Best Form of Vitamin B6?

Written by Andy Mobbs
featured image for seneca nootropic article on vitamin b6 Pyridoxal 5 Phosphate

Vitamin B6 is an incredibly important vitamin that’s involved in a huge range of functions in the body. Its active form – Pyridoxal-5-Phosphate (P5P) – is one of the key ingredients in our nootropic supplement, Seneca Nootropic Complex. Scroll down as we take a deeper look at this vitamin!

What is Vitamin B6 and what does it do in the body?

Vitamin B6 is an essential nutrient and one of the eight B-complex vitamins (B1, B2, B3, B5, B6, B7, B9, and B12). There are six forms of Vitamin B6 (1):

  • Pyridoxine (most commonly found in food and many dietary supplements)
  • Pyridoxal
  • Pyridoxamine
  • Pyridoxine-5-phosphate
  • Pyridoxal-5-phosphate (most biologically active form – more on this later)
  • Pyridoxamine-5-phosphate

Unlike some other vitamins, we cannot synthesize or make Vitamin B6. Instead, we get it from food sources, such as fish, liver, organ meat, starchy veggies, and fruits. Therefore, a diet rich in B6 is a must to avoid deficiency.

According to the European Food Safety Authority, Vitamin B6 contributes to the following (2):

  • Cysteine synthesis
  • Energy-yielding metabolism
  • Normal functioning of the nervous system
  • Normal homocysteine metabolism
  • Normal protein and glycogen metabolism
  • Normal red blood cell formation
  • Normal function of immune systems
  • Reduction of tiredness and fatigue
  • Regulation of hormonal activity

What is Pyridoxal-5-phosphate (P5P)?

Pyridoxal-5-phosphate is the active coenzyme form of B6 with the highest biological activity. P5P is also the most common measure of vitamin B6 blood levels in humans (3).

As a coenzyme, it’s involved in many P5P-dependent enzymes. This includes the synthesis of amino acids, amino acid metabolites, and neurotransmitters like dopamine, serotonin, GABA, and norepinephrine. P5P is also involved in the making of hemoglobin and the metabolism of fatty acids (4).

What are the main functions of Vitamin B6?

1) Transaminase Enzymes

B6 in its active form (P5P) is needed as a co-factor for all Transaminase enzymes. These enzymes catalyze the transformation of one amino acid into another amino acid. They do this by combining the amino acid with something called a-keto acid. a-keto acids are most commonly found in glycolysis and the Krebs cycle (e.g pyruvate) which are biochemical pathways that form the basis of energy production (5).

Probably the best-known Transaminase enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AST and ALT are both on the standard blood test and are often considered to be markers of liver function.

As well as being used for energy production, Transaminase enzymes are used in gluconeogenesis. This is the production of sugar from amino acids, which can then be transferred around the body for energy, as well as in the urea cycle so nitrogen can be safely removed from the body (5, 6).

pyridoxal-5-phosphate is used in energy production and transaminase enzymes

2) Glycogenolysis

B6 is also needed for the enzyme glycogen phosphorylase to work, which breaks down glycogen stores into readily usable glucose. Because B6 is needed to both break down glycogen into glucose and to produce glucose in gluconeogenesis, a B6 deficiency is associated with reactive hypoglycemia, which basically means low blood sugar (7).

A common symptom in reactive hypoglycemia is being able to fall asleep normally, but not being able to sleep through the night, due to low glucose levels not being able to fuel the brain fully until morning (it actually takes energy to sleep!). Even for people in full ketosis, the brain still needs some glucose, and low glucose levels due to B6 deficiency can be a problem for people eating a ketogenic diet.

3) Neurotransmitter Synthesis

B6 is also needed for the production of key neurotransmitters in cognitive functioning including dopamine, epinephrine, GABA, norepinephrine, serotonin, and melatonin. Together these neurotransmitters are vital for cognition, attention, memory, sleep, and relaxation. This is why every serving of Seneca Nootropic contains 4mg (or 235% of recommended daily value) of B6 in active P5P form.

Unfortunately, during any deficiency of B6 in the body, the B6 available will be prioritized for energy production, which means turning amino acids into keto acids via transaminase enzymes. This is because from an evolutionary point of view having sufficient energy is the most important thing to keep us alive, whereas cognitive function and sleep are less important to keep us alive in the present moment.

So it’s always important to make sure we always have enough B6 to ensure we are not downregulating the production of key neurotransmitters.

Related article: What are nootropics?

4) The Folate Cycle and the Methylation Cycle

Vitamin B6 also plays a key role in the folate cycle which allows the production of Purines and Pyrimidines which are used for the production of DNA, RNA, and ATP. The folate cycle also leads to the production of 5 MTHF which is used in the methylation cycle.

The methylation cycle is a really important biochemical pathway that allows methyl groups to be moved around the body. A methyl group is a very simple molecule made of one carbon and 3 hydrogen atoms. But methyl groups are vital for a whole range of functions in the body, including liver health, neurotransmitter production, detoxification as well as DNA production and gene expression.

The methylation cycle begins when methionine becomes S-Adenosyl methionine (SAMe). SAMe is the methyl group carrier, or as it’s sometimes called a methyl donor, which carries the methyl groups around the body. Once SAMe delivers the methyl groups its job is done, and it becomes homocysteine. The problem with homocysteine is if levels become too high it can become toxic.

High homocysteine levels, for example, have been associated with both neurodegeneration and cardiovascular disease (8). However, the body keeps homocysteine levels low by using 3 different pathways. Two of these pathways turn homocysteine back into methionine. The third pathway (called the Transsulfuration pathway) turns homocysteine into cysteine which can then be used to produce glutathione which is the body’s main antioxidant, or to produce pyruvate which can be used for energy production.

B6 is needed to produce 5 MTHF, which is used in one of the pathways that turn homocysteine back into methionine. B6 is also the main cofactor in the transsulfuration pathway which turns homocysteine into glutathione or pyruvate. So adequate B6 levels are vital for folate functioning and methylation.

Who is at risk for Vitamin B6 deficiency?

Deficiency is uncommon since B6 is readily available in many types of foods. However, certain groups may be prone to deficiency – vegans, alcoholics, the elderly, diabetics, those suffering from systemic inflammation, and those taking certain oral contraceptives and other medications (9-12). Fortunately, supplementing with B6 is possible, but ensure you make the right choice as not all B6 supplements are created equal!

What’s the best type of Vitamin B6 to supplement with?

When supplementing with B6, it’s really important to also choose products with the active form of B6 which is pyridoxal 5 phosphate (Seneca is a perfect example!). Many supplements will use the inactive form Pyridoxine. The problem is that when taken in large amounts (and large amounts are usually added to supplements), Pyridoxine can actually compete with the active form P5P at the B6 receptors. This means the inactive form can actually get into the B6 receptors by mistake, and because it’s inactive it won’t work, and this can result in an overall reduction of B6 activity (13).

Final words

A well-rounded diet rich in fruits and vegetables will ensure you meet the required daily intake for vitamin B6 and prevent a deficiency as well. And when it comes to taking Vitamin B6 in supplement form, make sure you choose the best and most active form Pyridoxal-5-phosphate to reap the many different benefits of B6!

References

(1) Wikipedia contributors. “Vitamin B6.” Wikipedia, 16 Aug. 2021, en.wikipedia.org/wiki/Vitamin_B6.

(2) Sante, D. “EU Register of Nutrition and Health Claims Made on Foods (v.3.6).” EFSA, 2021, ec.europa.eu/food/safety/labelling_nutrition/claims/register/public/?event=search.

(3) “Vitamin B6.” The Nutrition Source, 4 Sept. 2019, www.hsph.harvard.edu/nutritionsource/vitamin-b6.

(4) PubChem. “Pyridoxal Phosphate.” PubChem, 2021, pubchem.ncbi.nlm.nih.gov/compound/Pyridoxal-phosphate.

(5) Patrick J Stover and Martha S Field, Vitamin B-61, Adv Nutr. 2015 Jan; 6(1): 132–133.

(6) E F CALDWELL, E W MCHENRY, Vitamin B6 and urea formation, Arch Biochem Biophys. 1953 Jun;44(2):396-403.

(7) T Oka, N Komori, M Kuwahata, I Suzuki, M Okada, Y Natori, Effect of vitamin B6 deficiency on the expression of glycogen phosphorylase mRNA in rat liver and skeletal muscle, 1994 Feb 15;50(2):127-9.

(8) Alessandra F.Perna, DiegoIngrosso, Cinzia Lombardi, Filomena Acanfora, Ersilia Satta Concetta, Maria Cesare, Eleonora Violetti, Maria Maddalena Romano, Natale G. De Santo, Possible mechanisms of homocysteine toxicity, Kidney International, Volume 63, Supplement 84, May 2003, Pages S137-S140.

(9) “Office of Dietary Supplements – Vitamin B6.” NIH – ODS, 2021, ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional.

(10) Wilson, Stephanie M C et al. “Oral contraceptive use: impact on folate, vitamin B₆, and vitamin B₁₂ status.” Nutrition reviews vol. 69,10 (2011): 572-83. doi:10.1111/j.1753-4887.2011.00419.x

(11) Ulvik, Arve, et al. “Evidence for Increased Catabolism of Vitamin B-6 during Systemic Inflammation.” The American Journal of Clinical Nutrition, vol. 100, no. 1, 2014, pp. 250–55. Crossref, doi:10.3945/ajcn.114.083196.

(12) Massé, Priscilla G., et al. “Type 1 Diabetes Impairs Vitamin B6 Metabolism at an Early Stage of Women’s Adulthood.” Applied Physiology, Nutrition, and Metabolism, vol. 37, no. 1, 2012, pp. 167–75. Crossref, doi:10.1139/h11-146.

(13) Misha F.Vrolij, Antoon Opperhuizen, Eugène H.J.M.Jansen, Geja J.Hagemana, Aalt Bast, Guido R.M.M.Haenena, The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function, Toxicology in Vitro, Volume 44, October 2017, Pages 206-212